Summary information and primary citation
- PDB-id
- 6jq6; DSSR-derived features in text and JSON formats
- Class
- RNA
- Method
- X-ray (2.626 Å)
- Summary
- Hatchet ribozyme structure soaking with ir(nh3)6+
- Reference
- Zheng L, Falschlunger C, Huang K, Mairhofer E, Yuan S, Wang J, Patel DJ, Micura R, Ren A (2019): "Hatchet ribozyme structure and implications for cleavage mechanism." Proc.Natl.Acad.Sci.USA, 116, 10783-10791. doi: 10.1073/pnas.1902413116.
- Abstract
- Small self-cleaving ribozymes catalyze site-specific cleavage of their own phosphodiester backbone with implications for viral genome replication, pre-mRNA processing, and alternative splicing. We report on the 2.1-Å crystal structure of the hatchet ribozyme product, which adopts a compact pseudosymmetric dimeric scaffold, with each monomer stabilized by long-range interactions involving highly conserved nucleotides brought into close proximity of the scissile phosphate. Strikingly, the catalytic pocket contains a cavity capable of accommodating both the modeled scissile phosphate and its flanking 5' nucleoside. The resulting modeled precatalytic conformation incorporates a splayed-apart alignment at the scissile phosphate, thereby providing structure-based insights into the in-line cleavage mechanism. We identify a guanine lining the catalytic pocket positioned to contribute to cleavage chemistry. The functional relevance of structure-based insights into hatchet ribozyme catalysis is strongly supported by cleavage assays monitoring the impact of selected nucleobase and atom-specific mutations on ribozyme activity.